The prime objective of this proposal is to study the cellular mechanisms involved in the pacemaking action of the pyeloureter of the multicalyceal kidney of the pig and relate these to the physiology of urine transport. It is proposed that in vitro electrophysiological recordings be made at multiple sites in the renal pelvis to establish the ionic basis of calyceal smooth muscle activity and thereby determine the spatial distribution and spectra of pacemaking areas. In addition, it is proposed that in vivo investigations be conducted on pigs to determine the factors controlling the electrical and hydrodynamic coupling of the ureter to the renal pelvis and bladder. In the course of in vivo investigations the effects of perturbation of the pacemaker areas by selective surgical ablation, acute and chronic ureteral obstruction and infection will be examined. The ultimate objective of these studies is to apply the findings to the diagnosis and treatment of patients with obstructive uropathy, dilated ureters, and hydronephrosis.